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BACKGROUND: Glucose and fatty acid overload-induced glucolipid toxicity of pancreatic ß-cells is associated with the development of diabetes. Endoplasmic reticulum stress (ERS) plays an essential role in this process. Ghrelin, a peptide secreted by the pancreas, negatively correlates with oxidative stress. The study aimed to investigate ghrelin's role in glycolipid-induced ß-cell dysfunction and its possible mechanism. METHODS: Mouse insulinoma ß-cell, NIT-1 cells, were stimulated with high fat and high glucose to induce glucolipid toxicity. High fat and high glucose-induced NIT-1 cells were treated with acylated ghrelin (AG) or [d-Lys3]-growth hormone releasing peptide (GHRP)-6. Flow cytometry and Cell Counting Kit-8 (CCK-8) assay were performed to assess apoptosis and cell viability. The protein expression related to apoptosis, inositol-requiring kinase 1 (IRE1)/c-Jun N-terminal kinase (JNK) signaling, and ERS were investigated using western blot. Enzyme-linked immunosorbent assay (ELISA) was adopted to examine insulin's synthesis and secretion levels. RESULTS: Ghrelin treatment improved cell viability while inhibiting cell glucolipotoxicity-induced NIT-1 cell apoptosis. Ghrelin can promote the synthesis and secretion of insulin in NIT-1 cells. Mechanistically, ghrelin attenuates ERS and inhibits the IRE1/JNK signaling pathway in NIT-1 cells induced by glucolipotoxicity. CONCLUSION: Ghrelin improves ß-cellular dysfunction induced by glucolipotoxicity by inhibiting the IRE1/JNK pathway induced by ERS. It could be an effective treatment for ß-cellular dysfunction.
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Apoptose , Estresse do Retículo Endoplasmático , Endorribonucleases , Grelina , Células Secretoras de Insulina , Proteínas Serina-Treonina Quinases , Animais , Camundongos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/metabolismo , Grelina/farmacologia , Grelina/metabolismo , Glucose , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacosRESUMO
An uncrewed aerial vehicle (UAV) platform equipped with dual imaging cameras, a gas sampling system, and a remote synchronous monitoring system was developed to sample and analyze volatile organic compounds (VOCs) emitted from landfills. The remote synchronous monitoring system provided real-time video to administrators with specific permissions to assist in identifying sampling sites within extensive landfill areas. The sampling system included four kits capable of collecting samples from different locations during a single flight mission. Each kit comprised a 1 L Tedlar bag for measuring landfill VOC concentrations according to the TO-15 method prescribed by the US Environmental Protection Agency. The air sample was introduced into a Tedlar bag via pumping. A known volume of the sample was subsequently concentrated using a solid multisorbent concentrator. Following this, the sample underwent cold trap concentration and thermal desorption. The concentrated sample was then transferred to a chromatography-mass spectrometry system for separation and analysis. Since the anaerobic catabolism of organic waste is exothermic and emits VOCs, this study employed UAV thermal imaging to locate principal emission sources for sampling. Visible-light imaging helped identify newer or older landfill sections, aiding in the selection of appropriate sampling sites, particularly when surfaces were thermally disturbed by solar radiation. Field measurements were conducted under three meteorological conditions: sunny morning, cirrus morning, and thin cloud evening (2 h after sunset), identifying 119, 122, and 111 chemical species respectively. The sequence of total VOC concentrations measured correlated with the meteorological conditions as follows: cirrus morning > thin cloud evening > sunny morning. The results indicated that ambient temperature and global solar radiation significantly influenced daytime gas emissions from landfills. Evening thermal images, unaffected by solar heating, facilitated more accurate identification of major VOC emission points, resulting in higher VOC concentrations compared to those recorded in the sunny morning. VOCs from the landfill were categorized into nine organic groups: alkanes, alkenes, carbonyls, aromatics, alcohols, esters, ethers, organic oxides, and others. The classification was based on carbon-containing compounds (Cn, where the compound contains n carbon atoms). Alkanes were predominant in terms of Cn presence, followed by alcohols and carbonyls. Among the organic groups, organic oxides, particularly 2-heptyl-1,3-dioxolane, exhibited the highest concentrations, succeeded by alkenes. Sampling under cloudy conditions or in the evening is recommended to minimize the effects of surface temperature anomalies caused by solar radiation, which vary due to differences in land composition.
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Monitoramento Ambiental , Compostos Orgânicos Voláteis , Instalações de Eliminação de Resíduos , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análiseRESUMO
Elongation of very long-chain fatty acids protein 6 (ELOVL6) plays a pivotal role in the synthesis of endogenous fatty acids, influencing energy balance and metabolic diseases. The primary objective of this study was to discover the molecular attributes and regulatory roles of ELOVL6 in male Nile tilapia, Oreochromis niloticus. The full-length cDNA of elovl6 was cloned from male Nile tilapia, and was determined to be 2255-bp long, including a 5'-untranslated region of 193 bp, a 3'-untranslated region of 1252 bp, and an open reading frame of 810 bp encoding 269 amino acids. The putative protein had typical features of ELOVL proteins. The transcript levels of elovl6 differed among various tissues and among fish fed with different dietary lipid sources. Knockdown of elovl6 in Nile tilapia using antisense RNA technology resulted in significant alterations in hepatic morphology, long-chain fatty acid synthesis, and fatty acid oxidation, and led to increased fat deposition in the liver and disrupted glucose/lipid metabolism. A comparative transcriptomic analysis (elovl6 knockdown vs. the negative control) identified 5877 differentially expressed genes with significant involvement in key signaling pathways including the peroxisome proliferator-activated receptor signaling pathway, fatty acid degradation, glycolysis/gluconeogenesis, and the insulin signaling pathway, all of which are crucial for lipid and glucose metabolism. qRT-PCR analyses verified the transcript levels of 13 differentially expressed genes within these pathways. Our findings indicate that elovl6 knockdown in male tilapia impedes oleic acid synthesis, culminating in aberrant nutrient metabolism.
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Ciclídeos , Elongases de Ácidos Graxos , Animais , Masculino , Elongases de Ácidos Graxos/genética , Elongases de Ácidos Graxos/metabolismo , Ciclídeos/genética , Ciclídeos/metabolismo , Metabolismo dos Lipídeos/genética , Inativação Gênica , Fígado/metabolismo , Nutrientes/metabolismo , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica , Sequência de Aminoácidos , Clonagem Molecular , Acetiltransferases/genética , Acetiltransferases/metabolismo , Técnicas de Silenciamento de GenesRESUMO
OBJECTIVE: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). METHODS: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. RESULTS: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). CONCLUSION: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice.
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Doenças Inflamatórias Intestinais , Qualidade de Vida , Adulto , Humanos , Qualidade de Vida/psicologia , Qualidade do Sono , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/psicologia , Ansiedade/epidemiologia , Ansiedade/etiologia , Ansiedade/psicologia , China/epidemiologiaRESUMO
Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens.
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Galinhas , Estudo de Associação Genômica Ampla , Animais , Galinhas/genética , Estudo de Associação Genômica Ampla/veterinária , Genômica , Fenótipo , SorogrupoRESUMO
BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage â cohort (510 HCCs and 2074 LCs) and Stage â ¡ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage â cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage â ¡ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.
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Carcinoma Hepatocelular , Ácidos Nucleicos Livres , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/epidemiologia , alfa-Fetoproteínas , Estudos Transversais , Detecção Precoce de Câncer/métodos , Ultrassonografia/métodos , Cirrose Hepática/diagnóstico , Cirrose Hepática/complicações , Biomarcadores TumoraisRESUMO
The problems with the current food distribution system are laid forth in this study. Getting high-quality agricultural and food products to consumers is the goal of what is known as the "agri-food supply chain." Agri-food supply chain knowledge exchange and risk management culture are being studied, as is the effect of supply chain management methods on business success. We are seeing an increase in the regularity of supply chain interruptions. The recent supply chain interruptions and their associated consequences highlight the necessity for robust supply systems. The primary goal of this research is to examine the interplay between critical antecedents of the agri-food supply chain; supply chain resilience (including risk management culture); supply chain connectivity, visibility, collaboration, and agility; and the effect these factors have on supply chain resilience and, ultimately, firm performance. With the same foundational elements and backing from the literature, an empirical model has been suggested. From September 2020 to June 2021, 245 random samples were collected throughout Indonesia for this investigation. The suggested model and the interdependencies among the crucial antecedents have been verified using partial least squares-structural equation modeling (PLS-SEM). Findings from this study support the notion that agri-food supply chains benefit from increased emphasis on traceability, transparency, information sharing, and a culture of risk management. One major takeaway from this study is that by adopting the suggested methodology, businesses may build and strengthen their supply chain resilience capabilities by institutionalizing a risk management culture, raising employee risk awareness, and holding regular risk assessment drills. The study also suggests that businesses that want to strengthen their supply chains can do so by adopting information and communications technologies and visibility tools to improve their supply chain connectivity and visibility, allowing them to respond to and recover from disruptions in the supply chain more quickly. The model is validated using data from Indonesia's industrial sector. In order to establish supply chain resilience, the suggested model provides a comprehensive perspective that defines the interconnections between key antecedents. We conclude with some thoughts and suggestions for further study.
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Gestão do Conhecimento , Gestão de Riscos , Disseminação de Informação , Medição de Risco , AgriculturaRESUMO
Rice is the major source of arsenic (As) intake in humans, as this staple crop readily accumulates As in the grain. Identifying the genes and molecular mechanisms underlying As accumulation and tolerance is a crucial step toward developing rice with reduced As levels. We identified 25 rice genes that improve As tolerance in yeast cells by expressing a complementary DNA (cDNA) library generated from As-treated rice roots. Among them, a zinc finger-type transcription factor VASCULAR PLANT ONE- ZINC FINGER 1 (OsVOZ1) (OsVOZ1) conferred the most pronounced As tolerance. OsVOZ1 inhibits As accumulation in yeast via activation of As efflux transporter Acr3p by post-transcriptional modification in yeast. The Arabidopsis voz1 voz2 double-knockout mutant exhibited As hypersensitivity, altered As concentrations in various tissues, and reduced As transport activity via the phloem. Arabidopsis and rice VOZs were highly expressed in phloem cells in various tissues, which are critical for As distribution in plant tissues. The double-knockdown and single-knockout plants of OsVOZ1 and OsVOZ2 reduced As accumulation in their seeds. These findings suggest that rice and Arabidopsis VOZs regulate the translocation of As into tissues by regulating the phloem loading of this element.
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AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, but there are currently limited treatment options available. Therefore, it is necessary to research new treatment strategies. Zhuyu Pill (ZYP) is a well-known herbal recipe consisting of Huanglian (Coptidis rhizoma) and Wuzhuyu (Evodiae Fructus) that has been clinically used to treat NAFLD. This study aimed to investigate the impact of ZYP on NAFLD induced by a high-fat diet (HFD) and to identify its potential mechanism. METHODS: In this investigation, we used ZYP to treat a mouse model of NAFLD induced by an HFD. We conducted various analyses including assessment of serum biochemical indices, histological evaluation, fecal metabonomics analysis, western blot, and quantitative real-time polymerase chain reaction. RESULTS: ZYP effectively improved blood lipid levels and reduced inflammatory response in HFD mice, while also alleviating liver cell damage and lipid accumulation. Additionally, ZYP influenced the fecal bile acid (BA) metabolism profiles of HFD mice by inhibiting the signal transduction of ileal farnesoid X receptor (FXR) fibroblast growth factor 15 (FGF15), enhancing the expression of cytochrome P450 family 7 subfamily A member 1(CYP7A1), promoting BA synthesis and increasing the metabolic elimination of cholesterol. CONCLUSION: ZYP shows promise as a potential treatment for alleviating NAFLD by modulating BA metabolism through the FXR-FGF15-CYP7A1 pathway.
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PURPOSE: Positive lymph node (LN) is a key prognostic factor in radically resected gallbladder cancer (GBCA). However, only a few underwent an adequate lymphadenectomy, and the number and extent of lymph node dissection (LND) have not been standardized. This study aims to develop an en bloc and standardized surgical procedure of LND for GBCA under laparoscopy. METHODS: Data of patients with GBCA underwent laparoscopic radical resection using a standardized and en bloc technique for LND were collected. Perioperative and long-term outcomes were retrospectively analyzed. RESULTS: A total of 39 patients underwent laparoscopic radical resection using standardized and en bloc technique for LND except one case (open conversion rate: 2.6%). Patients with stage T1b had significantly lower LNs involved rate than patients with stage T3 (P = 0.04), whereas median LN count in stage T1b was significantly higher than that in stage T2 (P = 0.04), which was significantly higher than that in stage T3 (P = 0.02). Lymphadenectomy with ≥ 6 LNs accounted for 87.5% in stage T1b, up to 93.3% in T2 and 81.3% in T3, respectively. All the patients in stage T1b were alive without recurrence at this writing. The 2-year recurrence-free survival rate was 80% for T2 and 25% for T3, and the 3-year overall survival rate was 73.3% for T2 and 37.5% for T3. CONCLUSION: The standardized and en bloc LND permits complete and radical removal of lymph stations for patients with GBCA. This technique is safe and feasible with low complication rates and good prognosis. Further studies are required to explore its value and long-term outcomes compared to conventional approaches.
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Neoplasias da Vesícula Biliar , Laparoscopia , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Excisão de Linfonodo/métodos , Linfonodos/patologiaRESUMO
OBJECTIVES: To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs. METHODS: Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. RESULTS: In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. CONCLUSIONS: Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.
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Cardiopatias , Humanos , Sequenciamento do Exoma , China , Morte Súbita , MutaçãoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. METHODS: Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. RESULTS: An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genéticaRESUMO
Chlorophyll (Chl) f was recently identified in a few cyanobacteria as the fifth chlorophyll of oxygenic organisms. In this study, two Leptolyngbya-like strains of CCNU0012 and CCNU0013 were isolated from a dry ditch in Chongqing city and a brick wall in Mount Emei Scenic Area in China, respectively. These two strains were described as new species: Elainella chongqingensis sp. nov. (Oculatellaceae, Synechococcales) and Pegethrix sichuanica sp. nov. (Oculatellaceae, Synechococcales) by the polyphasic approach based on morphological features, phylogenetic analysis of 16S rRNA gene and secondary structure comparison of 16S-23S internal transcribed spacer domains. Both strains produced Chl a under white light (WL) but additionally induced Chl f synthesis under far-red light (FRL). Unexpectedly, the content of Chl f in P. sichuanica was nearly half that in most Chl f-producing cyanobacteria. Red-shifted phycobiliproteins were also induced in both strains under FRL conditions. Subsequently, additional absorption peak beyond 700 nm in the FRL spectral region appeared in these two strains. This is the first report of Chl f production induced by FRL in the family Oculatellaceae. This study not only extended the diversity of Chl f-producing cyanobacteria but also provided precious samples to elucidate the essential binding sites of Chl f within cyanobacterial photosystems.
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Clorofila , Cianobactérias , Filogenia , RNA Ribossômico 16S/genética , Clorofila/metabolismo , Cianobactérias/química , LuzRESUMO
Abstract Objective: This study aims to explore the effect and mechanism of miR-375 in Laryngeal Squamous Cell Carcinoma (LSCC) cell progression. Methods: LSCC cells (LSC-1 and TU177) were transfected with miR-375-mimic, miR-375-inhibitor or miR-375-mimic + oe-CST1. The expression of miR-375, CST1, MMP-2, and MMP-9 was measured. The effect of miR-375-mimic, miR-375-inhibitor or miR-375-mimic + oe-CST1 on cell biological functions, including cell proliferation, migration, invasion, and apoptosis, was also assessed. The potential relationship between CST1 and miR-375 was predicted by Jefferson software and validated by dual luciferase reporter gene assay. Results: Downregulated miR-375 expression was found in LSCC cells. Overexpression of miR-375 inhibited the viability and migration and promoted apoptosis of LSCC cells. Jefferson database and dual luciferase reporter gene assay confirmed that miR-375 directly targeted CST1. Over-expression of CST1 could reverse the anti-cancer effect of miR-375 overexpression in LSCC cells. Conclusion: Collected evidence showed that miR-375/CST1 axis was implicated in LSCC progression. Level of evidence: Level 3
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Objective: Renshen Baidu Powder (RBP) is a famous classic compound of traditional Chinese medicine (TCM) and is commonly used for treating ulcerative colitis (UC). However, the pharmacological mechanism of RBP in treating UC remains unclear. This study investigates the possible mechanism of RBP for UC treatment by network pharmacological analysis and rat validation. Methods: First, the main chemical constituents of RBP were identified using ultrahigh-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Then, we obtained targets of identified compounds from the SwissTargetPrediction database and targets associated with UC from GeneCards database. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the metabolism-related signaling pathways affected by RBP. Hematoxylin-eosin (HE) staining was used to observe the pathological change of colon in UC rats after treating RBP, and terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP Nick end labeling (TUNEL) staining was used to detect apoptosis after RBP treatment. The enzyme-linked immunosorbent assay (ELISA) was employed to evaluate cytokine levels of TNF-α, IL-1ß, and IL-6. The protein expressions of Bax, Bcl-2, PI3K, AKT, and NF-κB in colonic tissue were detected using immunohistochemistry (IHC). Real-time quantitative polymerase chain reaction (RT-QPCR) was employed to evaluate mRNA expression of PI3K, AKT, and NF-κB. Results: We found a total of 24 main compounds and 329 potential targets related to UC. According to KEGG results, 3 main pathways were identified as responsible for UC, including PI3K-AKT, HIF-1, and VEGF signaling pathway. Animal experiments showed that RBP treatment significantly attenuated colon damage in rats with UC. Mechanistically, RBP could inhibit PI3K/AKT/NF-κB pathway; decrease cell apoptosis; and downregulate the expression of TNF-α, IL-1ß, and IL-6. Conclusions: This study demonstrated that RBP may exert anti-inflammatory and antiapoptotic therapeutic benefits in UC by regulating the PI3K/AKT/NF-κB signaling pathways, providing a scientific basis for understanding the mechanism of RBP against UC.
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OBJECTIVE: This study aims to explore the effect and mechanism of miR-375 in Laryngeal Squamous Cell Carcinoma (LSCC) cell progression. METHODS: LSCC cells (LSC-1 and TU177) were transfected with miR-375-mimic, miR-375-inhibitor or miR-375-mimic+oe-CST1. The expression of miR-375, CST1, MMP-2, and MMP-9 was measured. The effect of miR-375-mimic, miR-375-inhibitor or miR-375-mimic+oe-CST1 on cell biological functions, including cell proliferation, migration, invasion, and apoptosis, was also assessed. The potential relationship between CST1 and miR-375 was predicted by Jefferson software and validated by dual luciferase reporter gene assay. RESULTS: Downregulated miR-375 expression was found in LSCC cells. Overexpression of miR-375 inhibited the viability and migration and promoted apoptosis of LSCC cells. Jefferson database and dual luciferase reporter gene assay confirmed that miR-375 directly targeted CST1. Overexpression of CST1 could reverse the anti-cancer effect of miR-375 overexpression in LSCC cells. CONCLUSION: Collected evidence showed that miR-375/CST1 axis was implicated in LSCC progression. LEVEL OF EVIDENCE: Level 3.
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Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica/genética , Linhagem Celular Tumoral , Proliferação de Células/genéticaRESUMO
OBJECTIVES: To study the clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children. METHODS: The medical data of 200 children with epilepsy who underwent a genetic analysis of epilepsy by the whole exon sequencing technology were collected retrospectively, of whom 9 children with epilepsy had 16p11.2 microdeletion. The clinical phenotype and genetic features of the 9 children with 16p11.2 microdeletion were analyzed. RESULTS: The detection rate of 16p11.2 microdeletion was 4.5% (9/200). The 9 children with 16p11.2 microdeletion were 3-10 months old. They experienced focal motor seizures with consciousness disturbance, and some of the seizures developed into generalized tonic-clonic seizures. The interictal electroencephalogram showed focal or multifocal epileptiform discharge, and all 9 children responded well to antiepileptic drugs. The 9 children had a 16p11.2 deletion fragment size of 398-906 kb, and the number of deleted genes was 23-33 which were all pathogenic mutations. The mutation was of maternal origin in 2 children, of paternal origin in 1 child, and de novo in the other children. CONCLUSIONS: 16p11.2 microdeletion can be detected in some children with epilepsy. Most of the 16p11.2 microdeletion is de novo mutation and large gene fragment deletion. The onset of 16p11.2 microdeletion-related epilepsy in children is mostly within 1 year of life, and the epilepsy is drug-responsive.
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Epilepsia , Anticonvulsivantes , Epilepsia/tratamento farmacológico , Epilepsia/genética , Humanos , Fenótipo , Estudos Retrospectivos , Convulsões/genéticaRESUMO
A few groups of cyanobacteria have been characterized as having far-red light photoacclimation (FaRLiP) that results from chlorophyll f (Chl f) production. In this study, using a polyphasic approach, we taxonomically transferred the Cf. Leptolyngbya sp. CCNUW1 isolated from a shaded freshwater pond, which produces Chl f under far-red light, to the genus Kovacikia and named this taxon Kovacikia minuta sp. nov. This strain was morphologically similar to Leptolyngbya-like strains. The thin filaments were purplish-brown under white light but became grass green under far-red light. The 31-gene phylogeny grouped K. minuta CCNU0001 into order Synechococcales and family Leptolyngbyaceae. Phylogenetic analysis based on 16S rRNA gene sequences further showed that K. minuta CCNU0001 was clustered into Kovacikia with similarities of 97.2-97.4% to the recently reported type species of Kovacikia muscicola HA7619-LM3. Additionally, the internal transcribed spacer region between 16S-23S rRNA genes had a unique sequence and secondary structure compared with other Kovacikia strains and phylogenetically related taxa. Draft genome sequences of K. minuta CCNU0001 (8,564,336 bp) were assembled into one circular chromosome and two circular plasmids. A FaRLiP 20-gene cluster comprised two operons with the unique organization. In sum, K. minuta was established as a new species, and it is the first species reported to produce Chl f and for which a draft genome was produced in genus Kovacikia. This study expanded our knowledge regarding the diversity of Chl f-producing cyanobacteria in far-red light-enriched environments and provides important foundational information for future investigations of FaRLiP evolution in cyanobacteria.
Assuntos
Cianobactérias , Clorofila/análogos & derivados , Cianobactérias/genética , Água Doce , Filogenia , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: Trauma experience increases the risk of suicidal ideation, but little is known about potentially psychological mechanisms underlying this relationship. This study aims to examine the relationship between coronavirus disease 2019 (COVID-19)-related traumatic event (CTE) exposure and suicidal ideation among hospital workers, and identify mediating roles of sleep disturbances in this relationship. METHODS: Workers in seven designated hospitals in Wuhan, China, were invited to participate in an online survey from May 27, 2020, to July 31, 2020. Participants completed a self-report questionnaire to evaluate demographic characteristics, level of CTE exposures, nightmare frequency, insomnia severity, symptoms of depression and anxiety, and suicidal ideation. A series of correlation analyses were performed, and a mediation model was generated to examine correlations between CTE exposure, sleep disturbances, and suicidal ideation. RESULTS: A total of 16,220 hospital workers were included in the final analysis, 13.3% of them reported suicidal ideation in the past month. CTE exposure was significantly associated with insomnia severity, nightmare frequency, and suicidal ideation. After controlling potential confounders, nightmares but not insomnia, depression, or anxiety were shown to be independent risk factors for suicidal ideation. Pathway analyses showed that the relationship between CTE exposure and suicidal ideation was fully mediated by nightmares (proportion mediated 66.4%) after adjusting for demographic characteristics and psychological confounders. LIMITATIONS: Cross-sectional design precluded the investigation of causal relationships. CONCLUSIONS: CTE exposure increases risk of hospital workers' suicidal ideation that is mediated by nightmares, suggesting nightmares intervention might be considered as a component when developing suicide prevention strategies.
Assuntos
COVID-19 , Distúrbios do Início e da Manutenção do Sono , Estudos Transversais , Sonhos/psicologia , Humanos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Ideação SuicidaRESUMO
Monosodium urate (MSU) crystals, the etiological agent of gout, are formed in joints and periarticular tissues due to long-lasting hyperuricemia. Although MSU crystal-triggered NLRP3 inflammasome activation and interleukin 1ß (IL-1ß) release are known to have key roles in gouty arthritis, recent studies revealed that MSU crystal-induced necrosis also plays a critical role in this process. However, it remains unknown what forms of necrosis have been induced and whether combined cell death inhibitors can block such necrosis. Here, we showed that MSU crystal-induced necrosis in murine macrophages was not dependent on NLRP3 inflammasome activation, as neither genetic deletion nor pharmacological blockade of the NLRP3 pathway inhibited the necrosis. Although many cell death pathways (such as ferroptosis and pyroptosis) inhibitors or reactive oxygen species inhibitors did not have any suppressive effects, necroptosis pathway inhibitors GSK'872 (RIPK3 inhibitor), and GW806742X (MLKL inhibitor) dose-dependently inhibited MSU crystal-induced necrosis. Moreover, a triple combination of GSK'872, GW806742X, and IDN-6556 (pan-caspase inhibitor) displayed enhanced inhibition of the necrosis, which was further fortified by the addition of MCC950 (NLRP3 inhibitor), suggesting that multiple cell death pathways might have been triggered by MSU crystals. Baicalin, a previously identified inhibitor of NLRP3, inhibited MSU crystal-induced inflammasome activation and suppressed the necrosis in macrophages. Besides, baicalin gavage significantly ameliorated MSU crystal-induced peritonitis in mice. Altogether, our data indicate that MSU crystals induce NLRP3-independent necrosis, which can be inhibited by combined inhibitors for multiple signaling pathways, highlighting a new avenue for the treatment of gouty arthritis.